A specific interaction between the telomeric protein Pin2/TRF1 and the mitotic spindle

Pin2/TRF1 was independently identified as a telomeric DNA binding protein ( TRF1) [1] and as a protein (Pin2) that can bind the mitotic kinase NIMA and suppress its ability to induce mitotic catastrophe [2, 3]. Pin2/TRF1 has b een shown to bind telomeric DNA as a dimer [3-7] and to negatively regulate telomere length [8-11]. Interestingly, Pin2/TRF1 levels are regulated duri ng the cell cycle, being increased in late G2 and mitosis and degraded as c ells exit from mitosis [3]. Furthermore, overexpression of Pin2/TRF1 induce s mitotic entry and then apoptosis [12]. This Pin2/TRF1 activity can be sig nificantly potentiated by the microtubule-disrupting agent nocodazole [12] but is suppressed by phosphorylation of Pin2/TRF1 by ATM; this negative reg ulation is important for preventing apoptosis upon DNA damage [13]. These r esults suggest a role for Pin2/TRF1 in mitosis. However, nothing is known a bout how Pin2/TRF1 is involved in mitotic progression. Here, we describe a surprising physical interaction between Pin2/TRF1 and microtubules in a cel l cycle-specific manner. Both expressed and endogenous Pin2/TRF1 proteins w ere localized to the mitotic spindle during mitosis. Furthermore, Pin2/TRF1 directly bound microtubules via its C-terminal domain. Moreover, Pin2/TRF1 also promoted microtubule polymerization in vitro. These results demonstra te for the first time a specific interaction between Pin2/TRF1 and microtub ules in a mitosis-specific manner, and they suggest a new role for Pin2/TRF 1 in modulating the function of microtubules during mitosis. (C) 2001 Elsev ier Science Ltd. All rights reserved.